Endotoxin-induced disseminated intravascular coagulation in rabbits: effect of recombinant hirudin on hemostatic parameters, fibrin deposits, and mortality.
We evaluated the effect of r-hirudin on an experimental model of disseminated intravascular coagulation (DIC) in rabbits, through the continuous infusion of 100 microg/kg/hr of Escherichia coli endotoxin for a period of 6 hours. r-Hirudin (0.05, 0.3, and 0.6 mg/kg/hr) as treatment, or saline solution as placebo, were administered simultaneously with endotoxin. Severe DIC in the endotoxin control group was shown by impairment in hemostatic parameters, kidney fibrin deposition, and a high mortality rate. Medium and high doses of r-hirudin led to an improvement in such DIC-related parameters as platelet numbers and fibrinogen and protein C concentrations. High-dose r-hirudin also reduced consumption of antithrombin III (ATIII). All doses of r-hirudin prevented decreases in tissue plasminogen activator (t-PA) and reduced the increase in plasminogen activator inhibitor-1 (PAI-1) activity observed at 2 hours after endotoxin administration. A significant reduction in kidney fibrin deposition was seen in medium- and high-dose r-hirudin groups. Additionally, the mortality rate in rabbits receiving medium- and high-dose r-hirudin was 10%, and that in rabbits receiving low-dose r-hirudin was 20%, as compared with a mortality rate of 70% in the control group. Protein C activity was significantly lower (p < 0.001) in nonsurviving rabbits. Moreover, there was a strong positive correlation (r = 0.68, p < 0.001) between protein C consumption and kidney fibrin deposition. We conclude that r-hirudin can be a useful drug in the clinical treatment of DIC.
Hermida
J
J
Laboratory of Vascular Biology and Thrombosis, School of Medicine, University of Navarra, Pamplona, Spain.
Montes
R
R
Páramo
J A
JA
Rocha
E
E
D000818:Animals; D001777:Blood Coagulation; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000401:mortality; D004731:Endotoxins; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis; D006487:Hemostasis; D006629:Hirudins / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D008297:Male; D010976:Platelet Count; D011486:Protein C / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology
D004731:Endotoxins; D006629:Hirudins; D011486:Protein C; D011994:Recombinant Proteins; D005337:Fibrin